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Chemical Compound Review

Lopac-R-140     4-amino-N-[2,6- bis(methylamino)pyrimidin- 4...

Synonyms: CHEMBL433461, SureCN678897, CHEBI:172170, CCG-205122, BPBio1_000551, ...
 
 
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Disease relevance of Ro 04-6790

  • In addition, AO reduced both food consumption and body weight and the later effect was also seen following Ro 04-6790, suggesting a role for the 5-ht6 receptor in the regulation of feeding [1].
 

Psychiatry related information on Ro 04-6790

  • 2. In non-quantified behavioural observations, animals treated with Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p) showed no overt behavioural signs except a dose-dependent reduction in locomotor activity and a behavioural syndrome of stretching, yawning and chewing [2].
  • A series of Ro-04-6790 analogues that penetrate the brain and specifically bind to 5-HT(6) receptors reversed scopolamine-induced retention deficit in a passive avoidance learning test [3].
 

High impact information on Ro 04-6790

  • Intrinsic activity of these 5-HT6 receptor ligands at a constitutively active human S267K 5-HT6 receptor in Cos-7 cells indicated similar efficacy (E(max), % over basal) for 5-HT (97), E-6801 (91) and E-6837 (100), while Ro 04-6790 (-33) and SB-271046 (-39) were equi-efficacious inverse agonists [4].
  • Pre-treatment with the non-competitive NMDA receptor antagonist MK-801 (0.05 mg kg(-1) i.p.) prevented the effect of Ro 04-6790 on delay-induced deficits in object discrimination [5].
  • Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790 [6].
  • In the present study, receptor binding revealed that the pharmacological properties of the mouse receptor are different from the rat and human receptor: Ro 04-6790 does not bind to the mouse 5-HT6 receptor, so all in vivo testing included in the present report was conducted in rats [7].
  • Neither the 5-ht6 AO (which reduced cortical [3H]-LSD binding sites by 10-16%) nor Ro 04-6790 affected acquisition, but both enhanced retention of the learned platform position such that rats spent significantly longer searching the trained platform position than any other area during the probe tests [1].
 

Biological context of Ro 04-6790

  • Furthermore, neither AO nor Ro 04-6790 had any effect on the time taken to reach a raised visible platform, indicating that visual acuity was unimpaired [1].
 

Associations of Ro 04-6790 with other chemical compounds

 

Gene context of Ro 04-6790

  • 6. These data suggest that systemic injection of the 5-HT6 antagonist, Ro 04-6790, produces a stretching behaviour that appears to be mediated by an increase in cholinergic neurotransmission in the CNS and which could be a useful functional correlate for 5-HT6 receptor blockade [2].
  • We replicated previous reports that 5-HT6 receptor antagonists produce a stretching syndrome previously shown to be mediated through cholinergic mechanisms, but Ro 04-6790 and SB-271046 failed to attenuate scopolamine-induced deficits in a test of contextual fear conditioning [7].

References

  1. A role for 5-ht6 receptors in retention of spatial learning in the Morris water maze. Woolley, M.L., Bentley, J.C., Sleight, A.J., Marsden, C.A., Fone, K.C. Neuropharmacology (2001) [Pubmed]
  2. Investigation of stretching behaviour induced by the selective 5-HT6 receptor antagonist, Ro 04-6790, in rats. Bentley, J.C., Bourson, A., Boess, F.G., Fone, K.C., Marsden, C.A., Petit, N., Sleight, A.J. Br. J. Pharmacol. (1999) [Pubmed]
  3. Role of 5-HT6 receptors in memory formation. Meneses, A. Drug News Perspect. (2001) [Pubmed]
  4. Efficacy of selective 5-HT6 receptor ligands determined by monitoring 5-HT6 receptor-mediated cAMP signaling pathways. Romero, G., Sánchez, E., Pujol, M., Pérez, P., Codony, X., Holenz, J., Buschmann, H., Pauwels, P.J. Br. J. Pharmacol. (2006) [Pubmed]
  5. 5-HT6 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation--an effect sensitive to NMDA receptor antagonism. King, M.V., Sleight, A.J., Woolley, M.L., Topham, I.A., Marsden, C.A., Fone, K.C. Neuropharmacology (2004) [Pubmed]
  6. Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790. Woolley, M.L., Marsden, C.A., Sleight, A.J., Fone, K.C. Psychopharmacology (Berl.) (2003) [Pubmed]
  7. An assessment of the effects of serotonin 6 (5-HT6) receptor antagonists in rodent models of learning. Lindner, M.D., Hodges, D.B., Hogan, J.B., Orie, A.F., Corsa, J.A., Barten, D.M., Polson, C., Robertson, B.J., Guss, V.L., Gillman, K.W., Starrett, J.E., Gribkoff, V.K. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  8. Characterization of Ro 04-6790 and Ro 63-0563: potent and selective antagonists at human and rat 5-HT6 receptors. Sleight, A.J., Boess, F.G., Bös, M., Levet-Trafit, B., Riemer, C., Bourson, A. Br. J. Pharmacol. (1998) [Pubmed]
 
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